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Blood. 2017 Jun 22;129(25):3379-3385. doi: 10.1182/blood-2017-02-767285. Epub 2017 May 3.

Predicting the higher rate of intracranial hemorrhage in glioma patients receiving therapeutic enoxaparin.

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Department of Medicine and.
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center and Center for Biomedical Informatics, Boston, MA; and.
Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.


Venous thromboembolism occurs in up to one-third of patients with primary brain tumors. Spontaneous intracranial hemorrhage (ICH) is also a frequent occurrence in these patients, but there is limited data on the safety of therapeutic anticoagulation. To determine the rate of ICH in patients treated with enoxaparin, we performed a matched, retrospective cohort study with blinded radiology review for 133 patients with high-grade glioma. After diagnosis of glioma, the cohort that received enoxaparin was 3 times more likely to develop a major ICH than those not treated with anticoagulation (14.7% vs 2.5%; P = .036; hazard ratio [HR], 3.37; 95% confidence interval [CI], 1.02-11.14). When enoxaparin was analyzed as a time-varying covariate, anticoagulation was associated with a >13-fold increased risk of hemorrhage (HR, 13.26; 95% CI, 3.33-52.85; P < .0001). Overall survival was significantly shorter for patients who suffered a major ICH on enoxaparin compared with patients not receiving anticoagulation (3.3 vs 10.2 months; log-rank P = .012). We applied a validated ICH prediction risk score PANWARDS (platelets, albumin, no congestive heart failure, warfarin, age, race, diastolic blood pressure, stroke), and observed that all major ICHs on enoxaparin occurred in the setting of a PANWARDS score ≥25, corresponding with a sensitivity of 100% (95% CI, 63% to 100%) and a specificity of 40% (95% CI, 25% to 56%). We conclude that caution is warranted when considering therapeutic anticoagulation in patients with high-grade gliomas given the increased risk of ICH and poor prognosis after a major hemorrhage on anticoagulation. The PANWARDS score may assist clinicians in identifying the patients at greatest risk of suffering a major intracranial hemorrhage with anticoagulation.

[Indexed for MEDLINE]

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